Wound dressing, manufacture and use

ABSTRACT

An autoadhesive wound dressing which having a pad of highly absorbent alginate fibers, one face of which is provided with an interrupted layer of a pressure sensitive adhesive. Such a dressing has the advantages that a separate dressing need not be used to secure the autoadhesive dressing and the autoadhesive dressing may be cut to fit an irregular wound.

This invention relates to wound dressings, their manufacture and use.More particularly, this invention relates to wound dressings comprisingan alginate pad and an adhesive layer, to the method of theirmanufacture by applying a water based adhesive to an alginate pad and tothe use of such dressings in treating wounds.

A number of alginate wound dressings are available comnercially.Alginate dressings have the virtue of being able to absorb significantamounts of wound exudate and help maintain the wound in a conditionwhich aids its recovery. It is frequently desirable to render thedressing autoadhesive by which it is meant that it can be located at thewound without reliance on a separate dressing. Because of the need tomaintain the absorptive properties of the dressing and because ofdifficulties in applying adhesives directly to known forms of alginatepads, the art has hitherto achieved autoadherence by providing thedressing with a peripheral flange which is coated with adhesive; forexample as described in European Patents 243,069 and 236,104. Suchdressings locate the alginate pad over the wound by adhering to the skinsurrounding the wound. They are rather difficult to manufacture and arenot easily cut to shape when i. is desired to match the dressing to theshape of an irregular wound.

A dressing has now been discovered which is absorbent, autoadhesive,capable of being manufactured without recourse to peripheral adhesivecoated flanges and which can be cut to shape if desired. Hitherto it hasnot been practical to provide alginate dressings with adhesive on thealginate itself because of processing difficulties and, moreimportantly, the relatively poor absorption properties that resulted.

Accordingly the present invention provides an autoadhesive wounddressing which comprises a pad of highly absorbent alginate fibres oneface of which has an interrupted layer of a pressure sensitive adhesive.

By "highly absorbent" with respect to the fibre it is meant that theywill absorb at least 40 g/g of deionized water. A suitable method ofdetermination is set forth hereinafter. Most aptly the alginate fibreswill be present in a pad that can absorb at least 60 times, more aptlyat least 80 times, for example 80-280 times its own weight, more aptly90 to 150 times for example about 120 times its own weight of deionizedwater.

It is the highly absorbent nature of the pad made from such fibres thatallows easy manufacture of the dressing. Previously alginate fibre padshave proved extremely difficult to provide with an adhesive layer but byusing a water based adhesive in conjunction with such a highly absorbentfibres a dressing with particularly desirable properties has beenproduced.

Because of their highly absorbent nature, the dressings of thisinvention are particularly suitable for use on exuding wounds such asulcer, burns or the like. When used to treat such wounds the dressingmay be cut to shape if desired and gently adhered to the surroundingskin. The dressing can be left in place for a considerable time as itpromotes a healthy wound healing environment.

Typically the pad is a wet-laid pad of fibres which if desired can beneedle-tacked or hydraulically entangled. miner amounts of fibres ofother material may also be present if desired but this is not generallypreferred. Most aptly the pad is 0.5 to 7.5 mm thick and is preferably 1to 5 mm thick, for example 1.5 to 3 mm thick. Typical dressing sizes arerectangular with sides of from 4 to 20 cm, for example 5×15 cm, 10×10 cmand the like although other shapes may be employed, for examplecircular, oval or the like.

The adhesive employed may be any suitable pressure sensitive adhesivesuch as a polyacrylate, polyether, polyurethane or the like. Preferablythe adhesive layer is derived from an aqueous based adhesive, forexample an emulsion adhesive such as aqueous polyacrylate emulsionadhesive.

The adhesive layer will be interrupted, that is it wil have aperturessufficient to permit the passage of exudate there through. The aperturesmay be in the nature of pores or of perforations, for example associatedwith fibres penetrating the adhesive layer, in which case a large numberof such perforations spaced over the surface of the dressing are mostapt, or the apertures may be in the regular pattern produced by using anadhesive layer that results from a printing or pattern spraying process.

One favoured aspect of this invention provides a dressing in which theadhesive layer is a porous layer over the whole of the effective area ofthe dressing.

The present invention provides a process for the preparation of adressing according to the invention which comprises applying a layer ofadhesive to a pad of highly absorbent alginate fibres in a manner whichresults in the layer becoming interrupted.

Most aptly this method comprises applying a water based emulsionadhesive to the pad. Surprisingly the highly absorbent nature of thefibres allows this process to be put into effect without the need forsubsequent drying stages which are energy demanding and which can have adeleterious effect on the fibres.

Most aptly the aqueous emulsion adhesive has a high solids content, forexample greater than 50% w/w, more favourably greater than 60% w/w andpreferably about 70% w/w.

The aqueous emulsion adhesive may be any skin compatible adhesive but ingeneral it is most suitable to employ a vinyl ether and/or acrylic basedadhesive. Preferably the adhesive is an acrylic adhesive and mostpreferably one which has an anionic type dispersion.

Such adhesives can be specially prepared by the skilled adhesive chemistor may be commercially obtained from adhesive manufacturers. A supplierof emulsion adhesives is BASF.

Suitable apertured layers may be obtained by such methods as applyingadhesive all over the surface and allowing or causing apertures to form,for example as is absorbed by the fibres, the resulting layer becomesporous, or by applying in a pattern, for example with a patterned rolleror by pattern spraying and the like. Such patterns often allow 10-15% ofthe surface of the pad to be adhesive free.

Generally the thickness of the adhesive layer will be about 10 to 40microns, more usually 20 to 30 microns, for example about 25 microns.

If desired the face of the dressing opposite to the adhesive layer maybe provided with a film layer, for example as described in WO 90/01954or EP 0 279 118. The film layer will be a moisture vapour permeable filmfor example a polyurethane, polyetherester or a polyether amide.Generally the polymers will be hydrophilic, for example as described inEP 0 279 118. Aptly such films will be from 15 to 50 microns thick, moreusually 20 to 30 microns, for example 25 microns. The film layer may beapplied directly to the surface of the alginate pad but more suitablywill be adhered by means of an adhesive, for example as described in WO90/01954 or EP 0 279 118. Such adhesives are preferably moisture vapourpermeable, for example an acrylic, polyurethane or polyether adhesive ofwhich acrylic adhesives are preferred.

The adhesive coated face of the dressing may be provided with aprotector in conventional manner, for example a silicone coated releasepaper may be employed.

The dressing of this invention will preferably be sterile and containedwithin a bacteria proof pack, for example a sealed pouch comprising forexample a conventional paper-plastics film laminate or a paper aluminiumfoil and plastic film laminate. The dressing may be sterilised withinthe pack in conventional manner, for example gamma or electronirradiation or ethylene oxide gas.

The preferred fibres employed in fabric according to the invention maybe characterised by reference to their unique thermal properties, inthat a plot of the first order derivative of percentage weight loss ofthe fibre with temperature against temperature has two maxima in therange of 100 to 400° C. (Fibres free of adhesive may be obtained byremoving some from the top of the dressing or by removing the adhesivefor example by treatment with dichloro methane).

In general, the two maxima in the plot of the first order derivative ofpercentage weight loss with temperature against temperature for a fibreaccording to the invention will fall within the range 200 to 300° C.,preferably 220 to 290° C.

In general, the two maxima in the plot of the first order derivative ofpercentage weight loss with temperature against temperature for a fibreaccording to the invention will fall within the range 200 to 300° C.,preferably 220 to 290° C.

FIG. 1 shows the thermogravimetric analysis (TGA) of an 80:20calcium:sodium alginate fibre prepared by conventional methods.

FIG. 2 shows the thermogravimetric analysis (TGA) of a fibre accordingto the invention, prepared from the same source material as the fibre ofFIG. 1.

FIG. 3 shows the variation of heat flow with temperature for aconventional 80:20 calcium:sodium alginate fibre and a correspondingfibre in accordance with the present invention.

FIG. 4 shows the thermogravimetric analysis of a conventional fibre, ahigh absorbency fibre according to this invention and such a fibretreated with calcium ions.

Thermogravimetric analysis was performed using a 2950TGA manufactured byTA Instruments, Delaware, U.S.A. Differential scanning calorimetry (DSC)was performed using a DSC7 manufactured by Perkin-Elmer.

It can be seen with reference to FIG. 2, that the first order derivativeof percentage weight loss with temperature has two peaks, one atapproximately 225° C., and one at a higher temperature approximately280° C.

Preferred alginate fibres employed in dressings according to the presentinvention can further be characterised in terms of their glasstransition temperature, and in a further or alternative aspect, thepresent invention thus provides an autoadhesive wound dressing whichcomprises a pad of alginate fibres on one surface of which is aninterrupted layer of adhesive wherein the fabric comprises alginatefibre characterised in that its glass transition temperature is lessthan 30° C., such as about 26° C.

As hereinbefore described preferred alginate fibres employed indressings of the present invention exhibit improved absorptiveproperties wherein the absorbency of the fabric is at least 40.0 gramsof deionised water per gram of fabric as measured with reference to atest method depicted in FIG. 5 appended hereto.

The alginate pad employed in the dressings of present invention aptlyhas an absorbency of at least 40 times its own weight of deionised waterand more aptly at least 60 times and most aptly at least 80 times itsown weight of deionised water. Typically the fabric has an absorbency ofmuch greater than this, for example 80 to 280 times its own weight, moreaptly 90 to 150 for example such as about 120 grams of deionised waterper gram of pad.

Alginate fibres employed in dressings according to the present inventioncan further be characterised in terms of their dielectric behaviour. Forpolymers the dielectric constant is dependent on the ease with which thepolymer orientates itself in response to an applied field and this is afunction of the structure of the polymer. The constant is most easilyexpressed in terms of the relationship between the in-phase andout-of-phase components of the dynamic field. This is conventionallyexpressed as Tan δ. Multiple peaks are normally recorded when measuringTan δ due to a variety of relaxation phenomena. We have found thatalginate fibres suitable for use in the fabrics of the present inventionhave Tan δ values in the range of less than 1 and up to 15 Hz.Conventional alginate fibres have Tan δ values of from 40 Hz to 7000 Hz.

Preferred alginate fibres suitable for use in a dressing according tothe present invention, are typically obtained by a process comprisingthe following steps:

(1) treating alginate fibres with a suitable acid so as to producefibres comprising approximately 90-98%, such as 95% -98%, alginic acidfibres;

(2) treating the alginic acid fibres with a saturated aqueous solutionof mono- or divalent cations;

(3) washing the fibres with water until imbibition of water by thefibres has effectively ceased;

(4) treating the fibres with a source of a cation capable of forming awater-soluble alginate salt.

The fibres used as starting material in step 1 may be conventionalsalted alginate fibres (for example sodium, calcium, mixedsodium/calcium fibres produced in conventional manner, for example from2-10% w/w solutions, for example 4% solution)

Most suitably the alginate fibres for use in step (1) are calciumalginate fibres.

Suitable acids for use in step (1) include acids capable of protonatingalginic acid and may include both organic and inorganic acids.Preferably, hydrochloric acid will be used. Preferably the resultingalginic acid fibres have at least 95% of the acid residues in theunsalted form.

Suitable mono- or divalent cations for use in step (2) include solutionsof sodium, potassium and magnesium cations. Preferably apharmaceutically acceptable monovalent cation is used, most preferably asodium ion.

Step (3) is preferably effected by washing the fibres in a stream ofdeionised water. Desirably step (3) may be discontinued when swellinghas ceased.

Cations capable of forming water-soluble alginate salts include, forexample, sodium, potassium, lithium, ammonium and magnesium cations.Preferably the source of a cation capable of forming a water-solublealginate salt used in step (4) is a source of sodium cations, morepreferably sodium carbonate. Other carbonates may be used in like mannerto produce the alternative salts.

Small quantities of other ions (for example zinc or silver) may bepresent in step (4) if desired but generally these may be included inthe fibre after completion of step (4) if their presence is required.

A method of treating the product of the above process to include otherions is to treat the product with an aqueous solution of a source of theions.

The fibres may be collected at the end of step (4) by filtration orother suitable method and may be dried, for example by treatment with avolatile drying agent, such as methyl alcohol, ethyl alcohol, isopropylalcohol, acetone and the like, and then drying in air. It is one of theadvantages of this invention that the highly absorbent fibres may bedried without losing their ability to be highly absorbent when rewetted.

The fibres may have any convenient length, for example a staple lengthof 0.25 to 25 mm, more usually 0.5 to 15 mm, favourably 1 to 12 mm andpreferably 1.5 to 10 mm.

For the most highly absorbent products to be obtained, large amounts ofdivalent ions such as calcium ions are not added at step (4) or later.

The fibres may be treated with an aqueous solution of a desired ion, forexample if it is desired to increase the calcium ion content treatmentwith a source of calcium ions such as a solution of calcium chloride maybe used. In such treated fibres the higher of the two maxima (thatgenerally found within the range 280-300° C.) tends to be reduced to ashoulder on the lower of the two maxima (that generally found with amaximum in the range of 200-250° C.). However, the skilled worker willappreciate that a shoulder represents a second peak and the two peaksmay be separately drawn using standard computer aided calculations ifdesired.

For the most highly absorbent products to be obtained, large amounts ofdivalent ions such as calcium ions are not added at step (4) or later.

Aptly the fibres have a staple length of 0.25 to 25 mm, mnore usually0.5 to 15 mm, favourably 1 to 12 mm and preferably 1.5 to 10 mm.

The alginate may be obtained from any convenient source, for example L.Hyperborea or Eclonia Maxima of which Eclonia Maxima is preferred.

The fibres prepared according to the above described process may bedried using conventional methods, for example, using acetone or hot airdrying.

Alginate pads used in the present invention may have medicamentsincorporated therein. Suitable medicaments include those which aidrecovery of wounds, for example an antifungal agent, an antibacterialagent, an angiogenesis promoting agent or the like. Favoured medicamentsinclude antifungal agents such as metronidazole, and antibacterialagents such as chlorhexidine, prepared by treating the fibres with anaqueous solution of the medicament or its salt.

It has further been found that hyaluronic acid can be incorporated intothe alginate fibres of the fabrics according to the present invention.

A suitable average molecular weight range for HA for use in thedressings of the present invention is 1.5×10³ to 2×10⁶, more preferablyabout 7.5×10⁴.

Incorporation of HA into the alginate fibres may be achieved bycontacting alginate fibres with an aqueous solution of HA followed by asuitable aqueous ionic solution, such as a solution of calcium,magnesium or zinc cations, preferably a solution of calcium cations,more preferably aqueous calcium chloride solution.

Alginates are produced by a variety of micro-organisms and marine algaewhich are the normal commercial source. The alginates being naturalmaterials show considerable variety but are characterised in being blockcopolymers, the individual monosaccharide units being arranged intogroups as blocks of mannuronic (M) and guluronic (G) residues. Inaddition to the repeating blocks each polymer chain can contain aproportion of alternating M and G monosaccharide units.

Suitably alginate fibres employed in the absorbent layer may be high Mor high G, typically 60-80% by weight M or G respectively. The alginatefibres may be high absorbent fibres substantially as hereinbeforedescribed.

In the event that a relatively low absorbency product is required someof the solubilising ions (generally sodium) can be replaced by aninsolubilising ion such as calcium. This may be achieved by treating theadhesive coated pad with a source of calcium ions such as a solution ofcalcium chloride. In such treated fibres the higher of the two maxima(that generally found within the range 280-300° C.) tends to be reducedto a shoulder on the lower of the two maxima (that generally foundwithin the range of 200-250° C.). However, the skilled worker willappreciate that a shoulder represents a second peak and the two peaksmay be separately drawn using standard computer aided calculations ifdesired. Thus the present invention also provides an autoadherentdressing which comprises a pad of alqinate fibre which contains calciumions in addition to sodium ions and which has two TGA maxima asdescribed herein, and a layer of pressure sensitive adhesive.

The alginate fibres according to the invention may also be formed into adressing using wet-laying techniques such as those conventional in thepaper industry. Conventional alginate fibres cannot be wet-laid usingconventional paper-making techniques. The ability of the fibres employedin the present invention to be wet-laid by conventional methodsrepresents an important advantage of the present fibres overconventional alginate fibres.

In the preparation of a pad of non-woven fabric, a cotton card may beused to form a web, which may then be cross-lapped, for example with aGarnet Bywater cross-lapper, and then needle punched in a Garnet Bywaterneedle loom. In the preparation of a pad of woven fabric, the precursoralginate fibres may be carded and then spun into a yarn, which can bewoven in a conventional loom. Alternatively, the fibres may be collectedin a spinning box, according to the method described in British PatentNo. 568177, and woven. In the preparation of a pad of knitted fabric,the fibres can be prepared as a continuous filament yarn, againaccording to the method described in British Patent No. 568177, which isthen knitted on a conventional knitting machine.

The absorbency of fabric according to the invention may be determinedaccording to the following method. The absorbent test sample (strip) maybe obtained from fibres prior to coating or from fibres obtained fromthe dressing.

TEST METHOD

The apparatus used in the determination of absorbency is depicted inFIG. 5, and consists of water bath 1 containing a 0.9% (w/w) deionisedwater, absorbent strip 2, burette 3, top-pan balance 4 and overflow 5.

The thickness of the absorbent strip 2 is substantially equivalent tothat of the dressing 7. The filter paper 8 has substantially the sameplanar dimensions as the dressing 7, but not necessarily the samethickness.

The apparatus is set up with the surface 6 of the saline solution orwater level with the top surface of the top-pan balance 4. The flow ofliquid from the burette 3 is then adjusted to approximately 1.5 ml perminure. The absorbent strip 2 is then saturated and placed between thebath 1 and the balance 4, as depicted in FIG. 2. The balance 4 is thentared. A weighed dressing 7 and filter paper 8 (cut to size) ispositioned as depicted in FIG. 2. Care must be taken to ensure that theedge of the absorbent strip 2 furthest away from the water bath 1 doesnot extend beyond the corresponding edge of the dressing 7, as shown inFIG. 2.

After six minutes the weight shown on the balance 4 is recorded. Thedressing 7 and filter paper 8 are then removed and any residual weighton the balance 4 noted.

Absorbency is determined on the basis of the following equation:##EQU1##

TEST METHOD 2

The Tan δ value of a fibre was determined by using a Thurlby ThandorTG502 sweep/function generator, a Teczronics 2212 digital storageoscilloscope and a capacitance test cell (plate area 16 squarecentimetres and fitted with a 22KΩ resistor). The material to be testedwas placed in a small engineers vice and the vice closed. The distancebetween the plates was measured using a vernier calliper and the earthconnection made between the vice and the earth terminal of thecapacitance test cell. The function generator and oscilloscope were thenconnected and the amplitude of the applied sinusoidal voltage measuredtogether with the voltage drop across the resistor and the phase anglebetween the applied voltage signal and current. The frequency of theapplied field was then altered and the measurements repeated for manypoints in the range 5 mHz to 5 MHZ.

DESCRIPTION 1

Calcium alginate fibre (4 g) (spun from 2-8% w/w, 4, 5 or 6% w/w,solution) was immersed in 1M hydrochloric acid (1 1) for 20-30 seconds.The degree of acid conversion was determined from the relativeintensities of the peaks at 1720 cm⁻¹ and 1600⁻¹ in the infraredspectrum, to ensure that the degree of conversion was in excess of 95%.The fibre was then washed with water and immersed in saturated salinesolution (2 1). The fibre was then chopped to the required staplelength. After cutting to the appropriate length the fibre was dispersedinto a stirred vessel containing deionised water (2 1). The fibres werewashed in a stream of running water until they swelled to their maximumextent and no sodium chloride could be detected in the eluent. Sodiumcarbonate solution (0.1 M) was then added in 1 ml aliquots whilstmonitoring the pH and conductivity of the medium. Care was taken toensure that the pH did not exceed 6.5. After the addition ofapproximately 12 mls of sodium carbonate solution (conductivity meterreading between 180 and 200 micro siemens), the material was filteredand dried with acetone followed by air drying.

DESCRIPTION 2

Fibre (14g) produced according to Description 1 were suspended indeionized water (800 cm²) and stirred. A 100 mesh nylon gauze disc wasplaced in the bottom of a Buchner funnel (diameter 24 cm²) and placed ontop of a Buchner flask attached to a vacuum pump. The fibre suspensionwas poured into the funnel and the water allowed to drain from the pad.Vacuum was applied to remove the remaining water and then released.Isopropanol (approximately 150 ml) was poured gently on to the fibre padand allowed to freely drain through the structure after which vacuum wasapplied to remove residual solvent. The pad was dried in an oven at 50°C. to constant weight.

EXAMPLE 1

An alginate fibre pad (10cm ×10 cm) prepared according to Description 1was spread with an aqueous emulsion polyacrylate adhesive (Acronal V205,70% solids) using a doctor knife to give a thin uniform layer. Theadhesive layer was allowed to dry in air and was then covered by arelease paper sheet. The resulting dressing was highly absorbent andcapable of adhering to skin and absorbing exudate.

(Acronal is a trade mark of BASF; Acronal V205 has a solids content of69±1%, a viscosity of 800-1600 mPas at 23° C. shear gradient 2505¹, amean particle size of about 0.6 microns, the dispersion type isanionic).

EXAMPLE 2

An alginate fibre pad as described in Example 1 was placed on theadhesive coated side of an adhesive coated polyurethane film (both fibreand adhesive layers approximately 20-20 micron thick). To the exposedsurface of the pad was applied an adhesive as described in Example 1which was subsequently covered with a release layer. EXAMPLE 3

Example 1 was repeated using Lutonal M42 in place of Acronal. LutonalM42 is a polyvinyl methylether. EXAMPLE 4

Tan δ values were measured according to Test Method 2 above for a rangeof fibre samples. The results were as follows:

    ______________________________________                                                         Peak 1   Peak 2   Peak 3                                       Fibre Hz Hz Hz                                                              ______________________________________                                        KALTOSTAT.sup.1  6449     1000     896                                          KALTOGEL.sup.2 578 416 46                                                     KALTOSTAT acid treated, 2929 541 54                                           neutralised and dried.                                                        Fibre prepared as in 0.056 0.018 --                                           Description 1.                                                              ______________________________________                                         .sup.1 commercially available calcium sodium alginate of high guluronate      content                                                                       .sup.2 commercially available calcium sodium alginate of high malluronate     content                                                                  

We claim:
 1. An autoadhesive wound dressing which comprises a pad ofhighly absorbent alginate fibres, wherein the alginate fibres have anabsorbency of at least 40 g of deionized water per gram of pad, one faceof which pad is provided with an interrupted layer of a pressuresensitive adhesive, wherein the alginate fibres are characterised byhaving a split maxima in the range of 100° C. to 400° C. in a plot ofthe first order derivative of percentage weight loss of the fibre withtemperature against temperature.
 2. An autoadhesive wound dressing asclaimed in claim 1 wherein the pad comprises alginate fibres which arecharacterised by having two maxima in the plot of the first orderderivative of percentage weight loss with temperature againsttemperature in the range of 200° C. to 300° C.
 3. An autoadhesive wounddressing as claimed in claim 1 wherein the alginate fibres arecharacterised by having a glass transition temperature of less than 30°C.
 4. An autoadhesive wound dressing as claimed in claim 1 wherein thepad comprises alginate fibres obtainable by a process comprising thefollowing steps:i treating alginate fibres with a suitable acid so as toproduce fibres comprising approximately 90-98% alginic acid fibres; iitreating the alginic acid fibres with a saturated aqueous solution ofmono- or divalent cations; iii washing the fibres with water untilimbibition of water by the fibres has effectively ceased; and ivtreating the fibres with a source of a cation capable of forming awater-soluble alginate salt.
 5. An autoadhesive wound dressing asclaimed in claim 4 wherein the alginate fibres in i are calciumalginate.
 6. An autoadhesive wound dressing as claimed in claim 4wherein other ions and/or medicaments are included after or during stepiv.
 7. An autoadhesive wound dressing as claimed in claim 4 wherein thefibres comprise hyaluronic acid or a pharmaceutically acceptable saltthereof.
 8. An autoadhesive wound dressing which comprises a pad ofalginate fibres which fibres contain calcium ions in addition to sodiumions, the fibres being characterised by having a split maxima in therange of 100° C. to 400° C. in a plot of the first order derivative ofpercentage weight loss of the fibre with temperature against temperatureand the dressing having a layer of pressure sensitive adhesive.
 9. Anautoadhesive wound dressing as claimed in claim 8 comprising a pad ofalginate fibres wherein the fibres are characterised by having a Tan δvalue in the range from 0 to 15 Hz.